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BERKELEY -- With the cosmetics industry facing a European ban on animal testing in 2009, a newly developed biochip could provide the rapid analysis needed to insure that the chemicals in cosmetics are nontoxic to humans.

BERKELEY -- With the cosmetics industry
facing a European ban on animal testing in 2009, a newly developed
biochip could provide the rapid analysis needed to insure that the
chemicals in cosmetics are nontoxic to humans.

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The
biochip, announced this week in the online edition of the Proceedings
of the National Academy of Sciences, is a suspension of more than a
thousand human cell cultures in a three-dimensional gel on a standard
microscope slide. Each cell culture is capable of assessing the
toxicity of a different chemical. According to researchers from the
University of California, Berkeley, Rensselaer Polytechnic Institute
and Solidus Biosciences, Inc. of Troy, N.Y., cultures of skin cells in
this so-called DataChip could be used to rapidly screen new chemicals
for skin toxicity or irritability.

By adding other types of cells, such as lung or heart
cells, and combining the DataChip with another biochip - the MetaChip -
that the researchers created several years ago, cosmetics or chemical
companies could also test whether chemicals are toxic to other organs,
not just skin.

"The DataChip expands the capabilities of the
MetaChip and enables it to test for toxic effects of chemicals and
their metabolites throughout the body," said co-lead author Douglas S.
Clark, UC Berkeley professor of chemical engineering and co-founder of
Solidus Biosciences, the company that is working to commercialize the
chips. "It is one step closer to a replacement for animals in
evaluating product safety, as well as to a personalized system that can
predict the toxicity of drugs in individual patients."

The
MetaChip that was reported two years ago contains liver enzymes
immobilized on a microscope slide. Liver enzymes can sometimes alter
seemingly safe chemicals and make them toxic. The MetaChip mimicks this
process, quickly metabolizing a chemical to produce compounds the liver
itself would produce. The DataChip provides an equally fast way to
determine the effect of these metabolites on cells.

For drug
companies, the combination of the MetaChip and the DataChip offers a
rapid way to predict whether a drug candidate or its metabolite is
toxic. The chips will also enable chemical companies to comply with new
legislation stipulating that chemicals undergo toxicity analysis.

"We
looked at the issues facing companies and realized that we needed to
develop something that was low-cost, high-throughput, easily
automatable and did not involve animals" said co-lead author and
Solidus Biosciences co-founder Jonathan S. Dordick, the Howard P.
Isermann '42 Professor of Chemical and Biological Engineering at
Rensselaer. "We developed the MetaChip and DataChip to deal with the
two most important issues that need to be assessed when examining the
toxicity of a compound - the effect on different cells in our body and
how toxicity is altered when the compound is metabolized in our bodies."

The
collaborative team sees the combined chips as an efficient, more
accurate way to test drug compounds for toxicity earlier in the
discovery process, before a lot of money has been invested in a drug
candidate. However, according to Clark, pharmaceutical companies are
only one potential user, and not necessarily the first.

"Obviously
cosmetics need to be safe, and ensuring the safety of new compounds
without testing them on animals presents a new challenge to the
industry, especially as the number of compounds increases," said Clark.
"These chips can meet this challenge by providing comprehensive
toxicity data very quickly and cheaply."

Within the next 5 to 10
years, assuming the cost of sequencing all of a person's genes becomes
generally affordable, people will be able to mine their personal
genomes for information on the types and levels of liver enzymes that
determine how they react to specific drugs and then reproduce this
profile on a MetaChip to prescreen all drugs before they're
administered to determine safe and effective doses.

The DataChip
currently contains 1,080 human cell cultures arranged within a gel made
of collagen or algae extract, approximating how cells are arranged in
organs of the human body. For now, the DataChip establishes a drug's
toxicity by whether it kills cells or inhibits their growth. Through
fundamental research, however, Clark and Dordick hope to adapt this
methodology to test for other biological responses, not just cell death.

"We
have the fundamental platform and concept, and there is the potential
to expand considerably beyond that to test for many different
biological responses, such as allergic responses or binding of a
chemical to a receptor to trigger a reaction," Clark said. "For
personalized medicine, that is exactly what you'd want to do."

Dordick
and Clark were joined in the research by Moo-Yeal Lee and Michael G.
Hogg of Solidus Biosciences; R. Anand Kumar of UC Berkeley; and Sumitra
M. Sukumaran of Rensselaer.

The research was funded by the National Institutes of Health and the New York State Office of Science and Technology (NYSTAR).